My previous work on cell-to-cell interactions in organogenesis revealed that nerve influences the growth and regeneration of embryonic parenchymal organs in culture. The synthetic activities of mixed aggregates of sensory nerve cells and cells from kidney and liver are far superior to that of each tissue cultured separately or mixtures of parenchymal and non-neural cells. Low concentrations of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) mimic the stimulatory effect of nerve on the growth and proliferaion of parenchymal tissue in vitro. The purpose of the proposed research is to elucidate some of the chemical and physical factors involved in growth regulation during organogenesis, and, more specifically, to detemine the mechanism by which nerve promotes regeneration of embryonic kidney and liver. The possibility that the growth promoting factor provided by nerve is either cyclic AMP or a substance that regulates cyclic nucleotide concentrations in the target cell will be investigated. Macromolecular changes during in vitro organ resynthesis in the presence and absence of nerve and chemical growth factors will be monitored. Any insight into the nature of integrative factors which regulate growth and tissue interactions during development is useful in that it may provide us with the tools necessary both to promote regrowth in organs which normally do not regenerate and also to inhibit the growth of cells whose control mechanisms are abnormal.